Cancer Reserach Update
Finding Zinc's Link to Cancer
March 7, 2012 | Issue 91

Also in this issue:

  1. In Brief: Cheap Beans and Cancer Risk
  2. It's the Calories, Not the Fructose
  3. Walnut-Eating Mice Show Less Prostate Cancer Growth
  4. Active Video Games Not So Active

Scientist in the Spotlight:
Finding Zinc's Link to Cancer Risk

Louise FongWhen Louise Fong, PhD, first began identifying how zinc deficiency affects esophageal cancer risk more than 30 years ago, the study of diet and cancer was only just beginning. Then at Massachusetts Institute of Technology, at the time it was unknown whether zinc deficiency could increase or decrease cancer risk.

What she saw in her lab research set Fong upon a path she would follow for the next several decades.

"I was amazed by the way zinc deficiency affected the esophagus," said Fong, now an associate professor at Thomas Jefferson University. "When the rats were on a zinc-deficient diet, the esophagus become very, very thick; the cells were multiplying, which is one of the hallmarks of cancer."

Like many nutrients, too much zinc or too little can cause health problems. The bluish-white metallic element is essential to a host of body processes, ranging from cell communication to maintaining our immune system. Zinc also appears to play a key role in the normal functioning of squamous cells, flat cells that line the esophagus, mouth and pharynx. The most common type of esophageal cancer develops in the squamous cells.

"The recommended dietary allowance for zinc is 11 mg for men and 8 mg for women. Red meat, poultry, oysters, nuts, fortified breakfast cereal, and dairy products are all good sources of the mineral."

AICR gave Fong her first grant on the topic in the early 1990s and continues to support her work. In a series of lab studies over the years, Fong and her colleagues have built up a body of evidence showing that zinc deficiency increases risk for esophageal and oral cancers, and that zinc supplementation may help prevent these cancers.

"In my previous work we could not really pinpoint a mechanism, now we can see the mechanism is chronic inflammation," notes Fong, referring to one of her recent studies published in Oncogene.

One big difference in this study, she says, is the amount of the carcinogen. In all her previous research, animals were exposed to a single low dose of a carcinogen. But Fong wanted to better mirror what humans experience: repeated low-doses of carcinogens, such as from smoking.

After giving rats three low doses of a carcinogen, about two-thirds of the animals eating a diet deficient in zinc developed esophageal squamous cell carcinoma. None of the animals eating a zinc-sufficient diet developed cancer. And compared to the cancer-free animals, Fong found high levels of activity in numerous cancer-related inflammation genes.

In many types of cancer, including esophageal and oral cancers, tumor cells exhibt abnormally high levels of COX-2, an enzyme linked to inflammation. Fong's studies have shown that in rats fed a zinc-deficient diet, high levels of COX-2 are accompanied by rapid cell division. When the rats were then fed a zinc-enriched diet, COX-2 levels dropped and cells stopped dividing rapidly. Exposure to a cancer-causing chemical caused tumors in the zinc-deficient rats but not in the rats with adequate zinc levels.

Fong and her coworkers have identified several genes that promote inflammation and are overproduced in zinc-deficient rats.

We need your help to advance cancer research, reduce America's cancer risk, and assist cancer patients and survivors. Please Give Now.We have shown that zinc deficiency causes unrestrained cell division in the esophagus and also that it increases inflammation," explains Dr. Fong. "Unrestrained cell division and inflammation create a precancerous condition that rapidly progresses to cancer when the animals are exposed to low doses of a cancer-causing chemical.

In other work focusing on oral cancer, Fong's research suggests that zinc supplements may also reduce cell proliferation and inflammation

"Animals receiving zinc supplementation developed fewer tumors and when tumors do occur they were smaller and less aggressive," she said

In the United States, zinc deficiency is uncommon overall, according to the Office of Dietary Supplements. Fong's research on zinc and cancer risk is promising but more research is needed to understand how zinc plays a role in cancer risk for humans.

"I want to understand the basis of zinc deficiency in cancer and this is not the entire story," says Fong. She is currently investigating the role of microRNA, a form of RNA that regulates gene expression. "This adds another layer of mechanisms."

Dietary zinc deficiency fuels esophageal cancer development by inducing a distinct inflammatory signature Oncogene. 2011 Dec 19. doi: 10.1038/onc.2011.592.

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legumes in briefIn Brief: Cheap Beans and Cancer Risk

For money savings on your plate, legumes and dry beans top the value list with many costing less than 20 cents per cup, according to a report released last year by the United States Department of Agriculture.

The report, How Much Do Fruits and Vegetables Cost?, found that the lowest average price for any of the 94 fresh and processed vegetables included in the study was for dry pinto beans, coming in at 13 cents per cup. A serving is about half a cup. (Fresh watermelon cost the least of the fruits surveyed, at only 17 cents per cup.)

Research shows that lentils, kidney beans and other legumes also play a role in reducing cancer risk. Visit AICR's Foods that Fight Cancer™ latest entry on Legumes to read how.


  • AICR's Foods that Fight Cancer™. Legumes (Dry Beans, Split Peas & Lentils) March 2012.
  • By Hayden Stewart, Jeffrey Hyman, Jean C. Buzby, Elizabeth Fraz„o, and Andrea Carlso. "How Much Do Fruits and Vegetables Cost? Economic Information Bulletin No. (EIB-71) 37 pp, February 2011. Full Report

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Research Roundup

It's the Calories, Not the Fructose

2 PeachesThe sugar that gives fruit its sweetness, fructose, will not make you gain any more weight than other forms of carbohydrates, finds a new review of the evidence. The review, published in the Annals of Internal Medicine, shows that extra calories – not any unique properties of fructose – are likely to lead to extra pounds.

Fructose, a carbohydrate, is found naturally in fruits and vegetables. The review addresses a handful of mixed studies investigating whether fructose has contributed to our country's obesity epidemic beyond that of other forms of carbohydrate.

For the review, researchers found 41 relevant trials conducted in settings where participants' food was controlled for at least seven days. None of the studies included high-fructose corn syrup or table sugar, which contains about half fructose bound with glucose. In 31 of the trials, participants ate a similar number of calories from proteins, carbohydrates and fats, but one group ate pure fructose and the other ate non-fructose carbohydrates. In the other 10 trials, one group added extra calories in the form of free fructose.

Fructose had no effect on weight when the diets had similar calories. When fructose added calories to the diet, there was a slight weight increase. But this may be attributable to the extra calories, not the fructose, the authors conclude.

These trials have many challenges and many did not mirror actual eating habits, note the authors, making the findings too preliminary to guide food choices.

Sources:Sievenpiper JL, de Souza RJ, Mirrahimi A, Yu ME, Carleton AJ, Beyene J, Chiavaroli L, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. "Effect of Fructose on Body Weight in Controlled Feeding Trials: A Systematic Review and Meta-analysis." Ann Intern Med. 2012 Feb 21;156(4):291-304.

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Walnut-Eating Mice Show Less Prostate Cancer Growth

walnutsA recent study in mice, published in the British Journal of Nutrition, found that the animals eating a diet containing whole walnuts had slower growing prostate tumors. The research, funded by the California Walnut Board, is being followed up in research supported by the American Institute for Cancer Research.

The study involved mice genetically programmed to develop prostate cancer. One group ate a diet containing ground walnuts; a second group ate a soybean oil diet, which matched the fat and nutrient levels of the walnut diet; the third group ate a low-fat diet. The amount of walnuts was approximately equal to a person eating three ounces, or three servings, of walnuts per day, the study notes.

Researchers measured prostate weight and tumor growth. After 18 weeks, the prostate weight of the walnut-fed and the low-fat diet groups were lower than that of the animals consuming their fat in soybean oil. No differences in weight were seen at 24 weeks. Overall, the rate of prostate tumor growth was 28 percent lower in the walnut-fed mice compared to the other groups.

Sources: Davis PA, Vasu VT, Gohil K, Kim H, Khan IH, Cross CE, Yokoyama W. "A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model." Br J Nutr. 2012 Jan 16:1-9. [Epub ahead of print]

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Active Video Games Not So Active

girl watching tvKids who play sports and other activity-based video games aren't getting any more physical activity than without those games, suggests a new study published in the journal Pediatrics.

The study builds on previous research showing that, in a lab setting, active video games can help kids be more active. But for this study, researchers tracked the activity level of about 80 kids in their homes over the course of three months.

Ages 9-12, the children were randomly assigned to get either two Wii active video games or two games that did not focus on activity. The active games included dancing, boxing, and skateboarding.

The children had the games for 13 weeks and for 5 of those weeks the researchers tracked their activity levels with an accelerometer, a device that measures motion. Study researchers also interviewed participants. At the end of the study, there was no evidence that the children who had the active video games were more active in general, or at anytime, than the kids who had the inactive video games.

Source: Baranowski T, Abdelsamad D, Baranowski J, O'Connor TM, Thompson D, Barnett A, Cerin E, Chen TA. "Impact of an Active Video Game on Healthy Children's Physical Activity." Pediatrics. 2012 Mar;129(3):e636-42. Epub 2012 Feb 27.

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